The expansion of urban and rural areas, together with the lack of adequate protection of river corridors, along with factors such as climate change, has severely threatened the water quality of these environments. Water Quality Indices (WQIs) are among the most efficient and effective tools for assessing the quality of surface and groundwater resources. This study was conducted to evaluate the water quality of the Sezar River in Lorestan Province using the Iranian surface water resources quality index (IRWQIsc) in conjunction with a Geographic Information System (GIS). In the first stage, based on the nine criteria defined for identifying major rivers within the national river restoration program, the importance and sensitivity of surface rivers in the province were assessed, and an overall importance–sensitivity coefficient was determined for all rivers in Lorestan Province. Given that the rivers within the Sezar Watershed were classified among those with high importance and sensitivity, the spatial integration of hydrometric station distribution and the river network resulted in the selection of five monitoring and sampling stations along the Sezar River. In this one-year study, water sampling and laboratory analyses were carried out at the selected stations during three seasons (summer, autumn, and winter of 2018) and the spring of 2019. To better illustrate spatial variations, longitudinal zoning of river water quality was performed in the ArcMap environment for all seasons based on the index values obtained at the monitoring stations. The results indicated that, according to the IRWQIsc, the water quality status of the studied river deteriorated throughout the hydrological year from autumn toward summer, with the lowest water quality conditions observed during the summer season.